Up to 15 per cent of those over age 65 years may be affected by symptomatic knee osteoarthritis (OA). In a recent NIH and AAOS- supported workshop whose goal was to develop research priorities for OA, natural history studies were recommended as a priority. As noted in the summary "identification of factors that affect the course of OA is a priority because patients .... at high risk of progression may benefit from treatments designed to prevent its advance." Our recent work from the Framingham OA Study suggests that intake of Vitamin C, an antioxidant and a cofactor in an enzyme necessary for collagen synthesis may prevent the progression of radiographic OA and also the onset of joint symptoms. Clinical trials have suggested a role for vitamin E in OA. We have recently reported that vitamin D, a factor with known effects on cartilage and bone, may influence OA progression. These results on effects of vitamin C & D need confirmation in other populations. Also, in recent work we have demonstrated that, compared to sedentary elders, those with higher physical activity levels are at high risk of developing radiographic OA, a finding with important implications for current recommendations for exercise as a treatment for OA. Lastly, MRI has permitted accurate visualization of a number of joint structures in which pathology may affect the risk of OA progression. These include localized trabecular bony uptake and meniscal loss or changes. Other studies of subjects with meniscectomies and longitudinal scintgraphic studies of bone uptake suggest that both of these factors may have important impacts on the likelihood of OA progression. The overall objective of this project is to evaluate the effect of three different types of factors: nutritional (vitamins C, E and D), physical and structural (as identified by MRI) on the natural of knee OA. The specific aims of this study are to: 1) To start a 30 month natural history study with 300 subjects composed on 150 veterans with OA currently followed and 150 newly recruited subjects. Risk factors (including MRI based ones) and outcomes will be assessed at baseline, 15 and 30 months. 2) assess the status of knee OA in two ways: by impact on function using WOMAC disability score and by loss in joint space using PA weight-bearing radiographs with fluoroscopy-based positioning. 3) evaluate nutritional factors including a) vitamin C and E intake estimated by food frequency questionnaire b) vitamin D status by measuring serum 25 - OH vitamin D. 4) assess physical factors by evaluating a subject's level of physical activity using validated questionnaires. 5) obtain MRI's to evaluate structural factors, specifically a) localized increased trabecular bone uptake, and b) meniscal loss or disease. 6) test the association between nutritional, physical and structural factors at a baseline and over follow-up with the change in OA status defined as change in disability or joint space loss over 30 months after adjusting for confounders. It is our hope that our study will identify factors that affect the progression of OA, factors that can be targets for later attempts at secondary or tertiary disease prevention.